The effects of agents which can perturb the cytoskeleton were studied in T lymphocytes from aging mice. Single cell suspensions of splenocytes and resting T cells were prepared from the spleens of young and senescent C57BL/6 mice. These populations of cells either were stimulated with the T cell mitogen, Concanavalin A, cytochalasin B and E, ionomycin, IL2 or various combinations of those or they were attached to cover slips for analysis of single cells. Levels of mitogenesis of the stimulated cells were assessed by tritiated thymidine incorporation. No age-related differences were observed in the activation of splenocytes and resting T cells by cytochalasin B. The highest levels of proliferation induced by Concanavalin A were unaffected by adding optimal concentrations of cytochalasin B, however, at nonoptimal Concanavalin A concentrations, cytochalasin B synergized resulting in 2-3 fold increases in proliferation of splenocytes and resting T cells from both young and old mice. Tritiated thymidine incorporation reached 40-60% of the maximal induced by Concanavalin A alone. These results suggest that cytochalasin B sensitive elements of the cytoskeleton such as actin are involved in T cell activation with no decrease in sensitivity in lymphocytes from older mice. The significance of this project is in understanding the possible role of cyto-skeletal components and growth factors in lymphocyte signal transduction and whether the observed decline in immune function with age can be attributed to alterations in cytoskeletal organization.